Heterocyclic substituted carboxylic acid derivatives useful for inhibit the binding of integrins to their receptors

摘要

A carboxylic acid derivative or a salt thereof has the formula (I) wherein: each Y is independently C(O), N, CR1, C(R2)(R3), NR5, CH, O or S; q is 3 to 10; A is O, S, C(R16)(R17) or NR6; E is CH2, O, S, or NR7; J is O, S or NR8'; T is C(O) or (CH2)b; b is 0 to 3; M is C(R9)(R10) or (CH2)u; u is 0 to 3; L is O, NR11, S, or (CH2)n; n is 0 or 1; X is CO2B, PO3H2, SO3H, SO2NH2, SO2NHCOR12, OPO3H2, C(O)NHC(O)R13, C(O)NHSO2R14, hydroxyl, tetrazolyl or hydrogen; W is =C-, -CR15 or N; each B and R1 to R17 are independently hydrogen, halogen, hydroxyl, or optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, nitro, amino, cyano, carboxy,-N(alkyl)-C(O)-alkyl), -NHC(O)N(alkyl)C(O)NH(alkyl), -NHC(O)NH(alkyl), alkylamino, alkenylamino, dialkylamino, -C(O)O-alkyl, -C(O)NH-alkyl, -C(O)N(alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, SO2-alkyl, SO3-alkyl, sulphonamido, carbamate, aryloxyalkyl, carboxyl or -C(O)NH-benzyl limited by the provisos as described in the specification. The compounds are useful for selectively inhibiting a4b1 integrin binding. Addition to 515248